During the past 40 years, clinicians interested in mood disorders have reported that a significant proportion of patients with endogenous depression also demonstrate a significant elevation in both plasma cortisol (hypercortisolemia) and in excretion of cortisol in the urine (hypercortisoluria). See Kathol, R. G., "Etiologic Implications of Corticosteriod Changes in Affective Disorder", Psychiatric Medicine 3, 135-162 (1985).
Moreover, these steroid changes appear to be related to the presence of active depression. That is, recovery from steroid abnormalities accompanies remission of the depressive symptoms. These, and other circumstances, has led to the supposition that corticosteroid changes are in some way related to the development of depression.
Cortisol is one of the adrenal cortical steroid hormones and these hormones are known to have significant effects on brain function and overall behavior. See McEwen, B. S., "Steroid Hormone Interactions with the Brain: Cellular and Molecular Aspects", Rev. Neuroscience 4, 1-30 (1979); Carpenter, W. T. and P. H. Gruen, J. Clin. Psychopharmacol. 2, 91-101 (1982).
Psychotic depressive episodes have been seen in patients with adrenal gland malfunctions such as Cushings Syndrome. See Kathol. R. G., Psychiatric Medicine 3, 135-162 (1985) for review. Moreover, mental disturbances sometimes occur in patients given cortisol. Clark, L. D. et al., New Eng. J. Med. 249, 178-183 (1953); Bunney, W. E. et al., Am. J. Psychiatry 122, 72-80 (1965).
The prevailing theory to explain these results is that a defect in the central nervous system (CNS) involving the hypothalamus-pituitary-adrenal gland (HPA) system causes cortisol hypersecretion in association with development of depressive symptoms. A controversy continues to exist, however, as to whether the hypercortisol secretion is primarily responsible for the observed psychopathology, or whether it is a secondary effect of the stress, weight loss, and altered sleep patterns of people with severe depression.